Measuring Altered Social Behavior in Neurodegenerative Disease

测量神经退行性疾病中社会行为的改变

• 批准号: 8699320
• 负责人: Katherine P Rankin
• 金额: $ 13.78万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-15 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8699320
• 关键词: Affect; Alzheimer' s Disease; Area; Behavioral; Biological; Biological Preservation; Caregivers; Cerebrovascular Disorders; Characteristics; Clinical; Cluster Analysis; Cognitive; Cognitive deficits; Corpus striatum structure; Data; Data Set; Dementia; Diagnosis; Diagnostic; Differential Diagnosis; Discrimination; Disease; Disease Progression; Early Diagnosis; Elderly; Emotional; Factor Analysis; Frontotemporal Dementia; Frontotemporal Lobar Degenerations; Genetic; Goals; Health; Impairment; Individual; Intervention; Interview; Investigation; Language; Lewy Body Dementia; Link; Magnetic Resonance Imaging; Measurement; Measures; Memory; Methods; Modality; Monitor; Motor; Neuroanatomy; Neurobehavioral Manifestations; Neurodegenerative Disorders; Neurologic; Neurologic Symptoms; Neuropsychological Tests; Outcome Measure; Patients; Pattern; Performance; Personality; Progressive Nonfluent Aphasias; Progressive Supranuclear Palsy; Proteomics; Questionnaires; Reporting; Research; Research Personnel; Semantic Dementias; Social Behavior; Social Change; Social Functioning; Symptoms; Systematic Bias; Testing; Time; base; behavior change; brain behavior; brain tissue; cerebral atrophy; clinical phenotype; cohort; computerized; corticobasal degeneration; diagnostic accuracy; disease diagnosis; disease phenotype; frontal lobe; improved; indexing; informant; insight; loss of function; morphometry; motor deficit; neuropsychological; normal aging; older patient; prognostic; social; social cognition; stability testing; tool; treatment trial

DESCRIPTION (provided by applicant): Changes in social behavior and personality are often the first symptoms of a neurodegenerative disorder, and eventually occur in the course of most dementias. However, no tools currently exist that have been validated to measure social behavior deficits in patients who have limited cognitive capacity and endurance for neuropsychological testing. The specific aim of this project is to adapt existing measures of social cognition for reliable and valid use in neurodegenerative diseases. The resulting battery will 1) operationalize the social criteria for frontotemporal lobar degeneration to improve early diagnosis, 2) identify characteristic patterns of social function in other dementias, 3) provide a valid, normed measure of social function in healthy older adults, 4) link quantitative data about social cognition with structural neuroanatomy. A five-year cross-sectional investigation will be performed with a cohort of 325 patients (50 Probable Alzheimer's, 50 Possible Alzheimer's, 50 frontotemporal dementia, 50 cerebrovascular disease, 25 semantic dementia, 25 progressive nonfluent aphasia, 25 dementia with Lewy-bodies, 25 progressive supranuclear palsy, and 25 corticobasal degeneration), as well as 100 healthy older controls as a normative reference group. Subjects' social behavior and cognition will be measured using multiple assessment modalities such as questionnaire- based informant reports, observational clinical ratings, and face-to-face measures of general and social cognition, including computerized testing. The social cognition battery will be validated to determine tests' item discrimination, internal consistency, practice effects, alternate form reliability, interrater reliability, and 1-year test stability. We will derive reliable change indices and a normative dataset of older adults' performance on each measure. We will also use cluster analysis to determine whether cognitive deficits in non-social domains such as memory, language, etc. exert a systematic bias upon the performance of any social test in the battery. Multitrait- multimethod matrices and factor analysis will be done to determine the construct validity of the tests when used both with healthy older adults and with neurodegenerative disease patients. Predictive validity will be tested using categorical discriminant function analysis to identify the patterns of social deficits that predict each diagnosis, and by using voxel-based morphometry of structural MRIs to determine if specific social symptoms correspond to expected patterns of regional brain tissue loss. The resulting battery could be used by clinicians 1) to aid in the differential diagnosis of dementia; 2) to provide treatment interventions, prognostic information, and caregiver support based on a patient's social symptoms; 3) to quantify changes in social function over time in individual patients. Researchers could use such a battery 1) to objectively quantify social behavior changes as an outcome measure in treatment trials, 2) to investigate the biological correlates (i.e., genetics, proteomics, neuroanatomy, etc.) of social behavior in groups of patients with neurologic conditions, 3) to carefully quantify social deficits in a variety of disease groups and thoroughly characterize each disease's clinical phenotype. PUBLIC HEALTH RELEVANCE: The primary goal of this project is to establish a psychometrically validated battery of social cognition and behavior measures that can be used with both healthy older adults and patients with neurodegenerative diseases. Having the right tests to recognize and objectively measure social symptoms will directly contribute to improved diagnosis of frontotemporal lobar degeneration-spectrum diseases, and will provide a means for clinicians to better characterize their patients' symptoms and measure disease progression. This measurement tool will also provide a unified means by which researchers can study social functioning in both normal aging and dementia, perhaps clarifying brain-behavior relationships or utilizing social symptom improvement as a valuable outcome measure in treatment trials.

描述（由申请人提供）：社会行为和人格的改变通常是神经退行性疾病的最初症状，并最终出现在大多数痴呆症的病程中。然而，目前还没有工具被证实可以测量神经心理测试中认知能力和耐力有限的患者的社会行为缺陷。该项目的具体目的是适应现有的社会认知措施，以可靠和有效地用于神经退行性疾病。由此产生的电池将1)操作额颞叶变性的社会标准以提高早期诊断，2)识别其他痴呆症的社会功能特征模式，3)提供健康老年人社会功能的有效规范测量，4)将社会认知的定量数据与结构神经解剖学联系起来。一项为期五年的横断面调查将对325名患者进行队列研究（50名可能的阿尔茨海默氏症患者，50名可能的阿尔茨海默氏症患者，50名额颞叶痴呆患者，50名脑血管疾病患者，25名语意性痴呆患者，25名进行性非流利性失语患者，25名路易体痴呆患者，25名进行性核上性麻痹患者，25名皮质基底变性患者），以及100名健康老年人作为标准参照组。受试者的社会行为和认知将采用多种评估方式进行测量，如基于问卷的信息报告、观察性临床评分、面对面的一般认知和社会认知测量，包括计算机化测试。社会认知电池将被验证以确定测试的项目歧视、内部一致性、实践效果、替代形式信度、被测者间信度和1年测试稳定性。我们将得出可靠的变化指数和老年人在每项措施上的表现的规范数据集。我们还将使用聚类分析来确定非社会领域（如记忆、语言等）的认知缺陷是否会对电池中任何社会测试的表现产生系统偏差。多特征-多方法矩阵和因子分析将用于确定健康老年人和神经退行性疾病患者测试的结构效度。预测有效性将通过分类判别函数分析进行测试，以确定预测每种诊断的社会缺陷模式，并通过基于体素的结构核磁共振形态学来确定特定的社会症状是否与预期的区域脑组织损失模式相对应。由此产生的电池可以被临床医生使用：1)帮助痴呆症的鉴别诊断；2)根据患者的社交症状提供治疗干预、预后信息和照护者支持；3)量化个体患者社会功能随时间的变化。研究人员可以使用这样的电池1)客观量化社会行为变化作为治疗试验的结果测量，2)研究神经系统疾病患者群体中社会行为的生物学相关性（即遗传学，蛋白质组学，神经解剖学等），3)仔细量化各种疾病群体的社会缺陷，并彻底表征每种疾病的临床表型。公共卫生相关性：该项目的主要目标是建立一套心理测量学验证的社会认知和行为测量方法，可用于健康老年人和神经退行性疾病患者。拥有正确的测试来识别和客观地测量社会症状将直接有助于改善额颞叶变性谱系疾病的诊断，并将为临床医生更好地表征患者的症状和测量疾病进展提供一种手段。这个测量工具也将提供一个统一的方法，研究人员可以通过它来研究正常衰老和痴呆症的社会功能，也许可以澄清大脑-行为的关系，或者利用社会症状的改善作为治疗试验中有价值的结果测量。